ACE2 Knockout Mice Are Resistant to High-Fat Diet-Induced Obesity in an Age-Dependent Manner
Abstract
:1. Introduction
2. Results
2.1. ACE2 Deficiency Decreases White Fat Depots and the Susceptibility to High-Fat Diet-Induced Obesity
2.2. ACE2 Deficiency Improved Glucose Control and Insulin Signaling
2.3. ACE2 Deficiency Leads to Impairment in Energy Balance
2.4. ACE2 Deficiency Did Not Alter Antioxidant Enzyme Activity in WAT
3. Discussion
4. Materials and Methods
4.1. Animals and Experimental Procedures
4.2. Glucose Tolerance and Insulin Sensitivity Tests
4.3. Metabolic Cage System
4.4. Body Composition Analysis
4.5. Lipolysis In Vivo and In Vitro
4.6. Euthanasia and Ex Vivo Experiments
4.7. Biochemical Analyses
4.8. Superoxide Dismutase (SOD) and Catalase (CAT) Activities
4.9. Adipose Tissue Histological Analysis
4.10. Quantitative Real-Time PCR
4.11. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Parameters | 6 Months | 12 Months | ||||||
---|---|---|---|---|---|---|---|---|
Standard Diet | High-Fat Diet | Standard Diet | High-Fat Diet | |||||
C57Bl/6 | ACE2-/y | C57Bl/6 | ACE2-/y | C57Bl/6 | ACE2-/y | C57Bl/6 | ACE2-/y | |
Muscle % | 67.77 ± 1.54 | 72.85 ± 1.78 | 48.11 ± 1.40 c | 64.85 ± 1.12 bd | 69.50 ± 0.74 | 72.84 ± 0.27 a | 49.92 ± 1.17 c | 51.85 ± 1.88 b |
Water % | 7.15 ± 0.11 | 7.34 ± 0.4 | 6.47 ± 0.13 c | 6.43 ± 0.18 b | 6.54 ± 0.19 | 6.71 ± 0.12 | 6.16 ± 0.11 | 6.54 ± 0.14 |
Triglyceride (mg·dL−1) | 22.02 ±1.9 | 16.57 ±2.3 | 26.9 ± 2.2 | 29.0 ± 1.7 b | 33.9 ± 3.3 | 32.9 ± 7.4 | 45.8 ± 6.0 | 44.9 ± 3.9 |
Cholesterol (mg·dL−1) | 36.97 ±2.1 | 45.23 ±4.4 | 126.3 ± 4.7 c | 140.7 ± 10.2 b | 68.1 ± 5.7 | 73.3 ± 12.6 | 173.6 ± 11.1 c | 210.3 ± 27.6 b |
NEFA (mmol·L−1) | 0.29 ± 0.03 | 0,14 ±0.01 a | 0.49 ± 0.05 c | 0.49 ± 0.05 b | 0.48 ± 0.1 | 0.27 ± 0.07 | 0.42 ± 0.04 | 0.42 ± 0.09 |
Glucose (mg·dL−1) | 121.6 ± 8.8 | 103.5 ± 7.0 | 153.0 ± 9.3 c | 165.2 ± 7.8 b | 138.8 ± 9.0 | 130.6 ± 6.6 | 187.8 ± 6.7 c | 176.8 ± 6.9 b |
Insulin (pg·dL−1) | 179.2 ± 12.2 | 175.7 ± 4.9 | 238.7 ± 25.8 | 184.1 ± 4.4 | 303.5 ± 6.8 | 301.2 ± 9.2 | 333.0 ± 17.5 | 331.1 ± 17.3 |
Food intake (g·day−1) | 5.12 ± 0.44 | 4.64 ± 0.15 | 4.57 ± 0.37 | 3.34 ± 0.18 bd | ND | ND | ND | ND |
Liquid intake (g·day−1) | 3.00 ± 0.3 | 4.27 ± 0.1 a | 2.61 ± 0.2 | 4.68 ± 0.4 d | ND | ND | ND | ND |
Total Energy Expenditure (kcal·h−1) | 0.55 ± 0.03 | 0.49 ± 0.01 | 0.58 ± 0.01 | 0.48 ± 0.01 d | ND | ND | ND | ND |
Primers | Sequence Forward and Reverse (5′–3′) and Length (bp) |
---|---|
Leptin | F: CGTGTGTGAAATGTCATTGATCCT (24) R: GACACCAAAACCCTCATCAAGAC (23) |
Adiponectin | F: GGAACTTGTGCAGGTTGGAT (20) R: CCTTCAGCTCCTGTCATTCC (20) |
Lipoprotein lipase | F: AGTGGCCGAGAGCGAGAAC (19) R: CCACCTCCGTGTAAATCAAGAAG (23) |
Hormone-sensitive lipase | F: ACGGATACCGTAGTTTGGTGC (21) R: TCCAGAAGTGCACATCCAGGT (21) |
Adrenergic β3 receptor | F: GCTGACTTGGTAGTGGGACTC (21) R: TAGAAGGAGACGGAGGAGGAG (21) |
Glucose transporter type 4 | F: TGATTCTGCTGCCCTTCTGT (20) R: GGACATTGGACGCTCTCTCT (20) |
Insulin receptor | F: CCACCAATACGTCATTCACAAC (22) R: GGGCAGATGTCACAGAATCAA (21) |
Glyceraldehyde 3-phosphate dehydrogenase | F: CCATCACCATCTTCCAGGAG (20) R: GTGGTTCACACCCATCACAA (20) |
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Nunes-Souza, V.; Alenina, N.; Qadri, F.; Mosienko, V.; Santos, R.A.S.; Bader, M.; Rabelo, L.A. ACE2 Knockout Mice Are Resistant to High-Fat Diet-Induced Obesity in an Age-Dependent Manner. Int. J. Mol. Sci. 2024, 25, 9515. https://doi.org/10.3390/ijms25179515
Nunes-Souza V, Alenina N, Qadri F, Mosienko V, Santos RAS, Bader M, Rabelo LA. ACE2 Knockout Mice Are Resistant to High-Fat Diet-Induced Obesity in an Age-Dependent Manner. International Journal of Molecular Sciences. 2024; 25(17):9515. https://doi.org/10.3390/ijms25179515
Chicago/Turabian StyleNunes-Souza, Valéria, Natalia Alenina, Fatimunnisa Qadri, Valentina Mosienko, Robson Augusto Souza Santos, Michael Bader, and Luiza Antas Rabelo. 2024. "ACE2 Knockout Mice Are Resistant to High-Fat Diet-Induced Obesity in an Age-Dependent Manner" International Journal of Molecular Sciences 25, no. 17: 9515. https://doi.org/10.3390/ijms25179515